PACE Trial and PACE Trial Protocol

re SMART targets: I was making fun of them when I was 15 and at school. They always seemed patronising and founded upon a foolish and unrealistic view of life.

I remember when I was at the CFS service being irritated by the fact that they seemed to be trying to portray my disinterest in this sort of approach to planning my life as indicative of some lack of motivation, rather than it being (as is my view) a reflection of my having a better understanding than them of how Britain's economy and labour market operate. I'd forgotten all about that irritation until just now... thanks Dolphin.

Talking of remembering related items – last night there was a piece on the local news about the primary schools in Medway where only 74% (I think) of students reached the expected level. This was all about the key stage assessments at age 11. I was teaching when these were all set up, and we had to define what was the average level for a child of 11, and this was called level 4. We were working on about the middle 40% being at level 4, then 30% above and 30% below. Well, surprise surprise, that is roughly what the figures are today. But now that it has been renamed the "expected level", suddenly everyone is expected to be average or above. Just like PACE and its use of "within normal function" as a label to mean "still pretty ill".

I have previously highlighted http://forums.phoenixrising.me/inde...st-bartholomew’s-barts-hospital-london.21076/ that there was a secondary outcome measure for recovery in the protocol for the £5m (taxpayer-funded) PACE Trial. However, a recent FOI request to Queen Mary, where Peter White is based, has revealed that the investigators do not intend to publish this data, nor release it to the person who made the FOI request.

There were three lead investigators in the PACE Trial, Peter White, Trudie Chalder & Michael Sharpe. I have previously highlighted how Peter White has recently (in a 2012 document) made recovery claims for the therapies.

This is an extract from a brochure for the service where Trudie Chalder is based (she is featured). This centre was one of the centres used in the PACE Trial. This is a April 2011 document (i.e. after the Lancet paper on the PACE Trial was published). [Aside: other people featured are Simon Wessely & Alastair Santhouse]

There were three lead investigators in the PACE Trial, Peter White, Trudie Chalder & Michael Sharpe. I have previously highlighted how Peter White has recently (in a 2012 document) made recovery claims for the therapies.

This is an extract from a brochure for the service where Trudie Chalder is based (she is featured). This centre was one of the centres used in the PACE Trial. This is a April 2011 document (i.e. after the Lancet paper on the PACE Trial was published). [Aside: other people featured are Simon Wessely & Alastair Santhouse]

I think it is curious that both Barts and Kings are claiming a 25% recovery rate. One theory I have is that this represents a natural recovery of patients with post viral fatigue. Katz and Jason reports 13% meeting CFS critria at 6 months 7% at 12 months and 4% at 24 following a viral infection (http://journals.lww.co/co-pediatri...e_syndrome_following_infections_in.99581.aspx). The cut from 13% to 7% is just under 50% as is the 7% to 4% but there will be people who don't get to their service.

The question is by being very unspecific, mainly relying of ill defined descriptions of fatigue and having no biomarkers are there two different things that are being combined and then doctors assuming treatments work.

He's looking at evidence for a parenting strategy known as 'Triple P', but his criticism of the lack of a proper control group applies equally to the PACE Trial.

31/ 33 studies compared Triple P interventions with waiting list or no-treatment comparison groups. This suggests that Triple P may be better than doing nothing with these self-referred families, but doesn’t control for simply providing attention, support, and feedback. The better outcomes for families getting Triple P versus getting than wait list or no treatment may reflect families assigned to these control conditions registering the disappointment with not getting what they had sought in answering the media ads [aka enrolling in the trial].

In contrast, the two studies involving an active control group showed no differences between groups.

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In PACE there was no appropriate control for attention/support: patients either had 'Specialist Medical Care' (SMC) or SMC plus a therapy such as CBT. There was no control for the generic placebo effect (or possible self-report bias). And PACE reported a strong difference in patient attitudes to being assigned to the different groups:

CBT: 71% thought it logical, 57% had confidence in it and the therapeutic alliance was scored as an average of 6.5 ex 7.

SMC: 49% thought it logical, 41% had confidence in it and there was no therapy so no score for a patient-therapist alliance.

This might explain, at least in part,why patients in the CBT group reported greater improvement in fatigue and function than those in the SMC group - while showing no improvement in the more objective 6-minute walk test.

However, the defence to this argument is that the Pacing therapy, APT, was even more popular with patients yet scored no better than SMC. This suggests strong patient preference for a therapy didn't impact on outcome scores.

APT: 84% thought it logical, 72% had confidence in it and the therapeutic alliance was scored as an average of 6.5 ex 7.

Perhaps this could have been because the ultra-cautious "70% Rule" used in the trial (of not exceeding 70% of perceived limits) actually put those in the APT group at a disadvantagecompared to the SMC group. But I would love to see this issue explored in a bit more depth in this thread as I think PACE have already used the defence above.

Think I may have posted a similar point before, but without getting any response, so trying my luck again.

"Waiting list is frequently employed as an ethical ’no treatment’ condition, to ensure that all participants eventually receive the ’active’ treatment. This approach was used in almost half of all studies comparing CBT against usual care. However, sub-group analyses showed that, at post-treatment, waiting list patients had reduced fatigue symptoms equivalent to those of patients attending for treatment. A possible explanation is that being on the waiting list for treatment had a ’holding’ positive influence, decreasing the apparent effect of the CBT intervention."

I always only refer to 'SMC' as the 'control', but one point to remember about the PACE Trial, is that the APT group was designed to be used as a control group, as well as the SMC group. So I think that complicates things a little when discussing the PACE Trial control. Maybe APT wasn't a well-designed control, but (unlike SMC) there were as many sessions of APT as there were for CBT/GET.

I probably should understand this but can't see this at the moment: what do they mean by "'holding' positive influence" in this context?

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I'd say they mean that being on the waiting list for treatment gives one hope, unlike being told that there is nothing that can be done. They believe this hope contributed to some improvement in this group. They would have preferred if the waiting list group made no change because it would have made CBT look better.

Of course they completely overlook the evidence that many improve spontaneously over time anyway. To test their hypothesis they would have needed a third group that were told nothing could be done for them.

Of course they completely overlook the evidence that many improve spontaneously over time anyway. To test their hypothesis they would have needed a third group that were told nothing could be done for them.

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Yes and, in particular, I think some people are inclined to improve when they actually have been given a diagnosis (and thus may be able to take time off work, get more support from family, etc (as opposed to people who haven't been given a diagnosis over the same period)). And probably in the year or so after being given a diagnosis is probably when the diagnosis will make more difference - and often people will be put on a waiting list after getting a diagnosis.

This reminds me of the study that is quoted to show CBT helped grey matter volume (De Lange et al.). There was no CFS control group. They used a sort of sleight-of-hand, in my mind by comparing to changes in the grey matter changes in healthy controls and inferring from this that it must have been the CBT that made the difference. (It could even be helped by the CBT, but not for the reasons given e.g. people rest more frequently).

I always only refer to 'SMC' as the 'control', but one point to remember about the PACE Trial, is that the APT group was designed to be used as a control group, as well as the SMC group. So I think that complicates things a little when discussing the PACE Trial control. Maybe APT wasn't a well-designed control, but (unlike SMC) there were as many sessions of APT as there were for CBT/GET.

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I thought that SMC and APT were sold as management strategies to help relieve symptoms where as CBT and GET were being pushed as cures. If I'm right I would have thought the placebo effects would be different

I thought that SMC and APT were sold as management strategies to help relieve symptoms where as CBT and GET were being pushed as cures. If I'm right I would have thought the placebo effects would be different

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Yes, agreed. APT may not have been a suitable control for a variety of reasons. But if we are ever making a reference to the number of sessions of SMC being less than CBT and GET, then I think it might be worth remembering that APT was also proposed as a control.

I'm not sure at this point has been made before.
But no harm mentioning it again.

The requirement to drop by 20 points or more on the SF-36 PF scale (compared to baseline) for a physical functioning reduction to be recorded could perhaps be seen as in effect a requirement for a bigger drop than 20 points as with SMC alone, the individuals might have expected to go up by a reasonable number of points e.g. baseline SMC: mean: 39.2, 12 months: mean: 50.8 i.e. average change of 11.6.
So a drop of 20 or more in SMC+GET, SMC+CBT or SMC+APT, is a bit like a drop of 31.6 or more.

So for example, somebody could get to 50 but drop to 20/25/30 but this wouldn't be counted. Or they could drop to 10 or 15 but then because of SMC get up to 20 or 25 and not meet the 20-point drop requirement, but still be a long way from what they could have expected to be at if they hadn't done CBT/GET/APT.

This is on top of the fact that they changed the rules to requiring a drop of 20 or more at consecutive time points.
The published protocol had:

"An adverse outcome will be considered to have occurred if the physical function score of the SF-36 [28] has dropped by 20 points from the previous measurement. This deterioration score has been chosen since it represents approximately one standard deviation from the mean baseline scores (between 18 and 27) from previous trials using this measure [23,25]."

I might have got it wrong, but that was my interpretation, re APT being used as a control. (as well as a treatment.)
I thought I'd seen it mentioned explicitly somewhere, but this is what I've found having a quick look, just now:

6. Failure to “control” (page 24)A control condition in an experiment or trial means an appropriate comparator. Both the paper and protocol explain that this trial was designed to compare effectiveness across treatment arms, with particular comparisons being prespecified; for each comparison of two treatments, one functioned as the control.